Market Complaint -Stages of Handling

A market/consumer complaint is a notification that a product is in commercial distribution (which also includes a physician sample). it May be in violation of the laws or regulations administered by the FDA (Drug Control Authority) or May have caused an illness, injury, or death and Is alleged to have caused problems not covered by the above. A complaint is an objection to something that is unfair, unacceptable, or otherwise not up to normal standards. Complaints may be about Services, Delivery, Quality of Product, Communication, Response, Time, Documentation, Billing, Follow up, etc. The complaint is any communication written or verbal, received directly from any customer, retailer, distributor, or representative of the contract giver, regarding the quality attributes, labeling defects, or any other matter such complaints shall be considered market complaints.

What are the stages of handling complaints?

The stages of handling complaints are as follows

• Receipt of complaint
• Categorization of complaint
• Notification to a regulatory agency,
• Initiating investigation
• Receipt and handling of samples,
• Risk Assessment and CAPA,
• Closure of the complaint,
• Trending,
• Historical review

PHENYLPROPANOLAMINE TABLET AND IT USES

Who is responsible for Receipt and handling of complaints?

The following personnel is responsible for the Receipt and handling of complaints as follow –

• Site QA must receive the complaint.
• Site QA must log the complaint within one (01) working day.
• Complaints can be shared with PV if the nature includes ADR/ADE or a combination of these with
  product quality.
• The complaint number must be assigned by site QA. If the number of complaints is more than one (01) from the same complainant and for different products, different numbers shall be assigned for each complaint.
• Site QA must acknowledge the receipt of the complaint with the complainant within three (03) working
  days through the company’s procedure.
• Additional information, if required, with photographs and samples can be obtained from the complainant. Annexure (“Information from complainant”) can be obtained from the complainant.

Question: Who is responsible for the Categorization of the complaints?

Answer :

Categorization of the complaints

• Site QA must categorize the complaint initially as critical or non-critical based on the nature of the complaint.
• The site QA Head must confirm the categorization of the complaint.

Preliminary investigation

A preliminary investigation can be performed for critical complaints within three (03) working days
from complaint awareness date.
Regulatory notification

• Alert Notification/FAR can be filed by site QA with the respective regulatory agency within three (03) working days from the complaint awareness date. The AN/FAR must include the preliminary investigation report.
• The Corporate Quality Head can be notified of the AN/FAR.
• All the batches/lots/markets likely to be impacted must be mentioned in the AN/FAR.
• Follow-up reports and final AN/FAR can be filed along with the interim and final investigation reports respectively as per the commitment given in the initial AN/FAR.
• The site QA Head must also report in a timely manner to the marketing authorization holder/sponsor and all Competent Authorities concerned in the matter about the detection of counterfeit, recall of the product, or an abnormal restriction in the supply of the product.

Investigation

• Complaints involving product quality can be investigated with cross-functional teams, wherever applicable, as per the investigation procedure of the company.
• If the complaint is critical in nature, the preliminary investigation must be completed within three (03) working days.
• Investigation can be performed as per the investigation procedure of the company.
•  Investigation can be performed by adopting suitable tools like fishbone analysis/Ishikawa, 5-Whys analysis, brainstorming, etc.
• Retention samples, complaint samples, input materials, and any other samples as applicable will be subjected to investigation.
• Batch records, in-process records, analytical records, stability data as applicable, and all allied records must be reviewed as part of the investigation.
• A historical review of product complaints/deviation/incidents/investigations can be carried out to establish the potential impact of market complaints on the concerned batch/other batches of the same product/substance and/or other manufactured products.
• A historical review of complaints from the previous two years (from the date of receipt of the complaint) can be performed.
• Additional experiments, if required, may be carried out with the help of relevant cross-functional departments to establish the root cause of the defect as per the approved study protocol.
• Investigation of batches of the drug product/drug substance manufactured using the same raw material/key starting material/packing material of the complaint batch must be performed and if it leads to possibly faulty equipment, the equipment may be subjected to investigation. Annexures for individual dosage forms/drug substances are given as attachments.
• If preliminary investigation points to raw material(s), key starting material(s), and/or packing material(s) as likely cause of complaint, the balance stock material of the respective QC reference number used in the complaint batch can be quarantined till the completion of the investigation.
• Quarantine may be effective until clearance to use is given by Site QA.
• Investigation can be extended to all batches of the same or other drug product/substance manufactured during the period in which the complaint batch was manufactured and impact assessment must be performed irrespective of whether the other batches were distributed or not.
• Health Hazard Evaluation can be performed for the complaints covering the following, wherever applicable, but not limited to, product/strength mix-up, a drug not available to the patient due to dissolution failure, degradation of the product, etc.
• Alert Notification/FAR can be communicated to the Regulatory Agencies within three (03) working days of detecting the defect irrespective of the stage of the investigation.
• All customers must be notified about the defect within three (03) working days in case of the drug substance.
• The complaint/s due to counterfeiting can be assessed and if the sample is found to be counterfeit in nature, Marketing, QA/RA, and Regulatory Agencies in countries where the product is distributed must be informed for appropriate action.
• Risk assessment can be carried out taking into account system failure during the investigation. It could be performed as per the QRM procedure.
• Risk Assessment for market complaints can be based on severity and occurrence.
• The evaluation of risk to the quality of the drug product/substance can be assessed based on scientific knowledge and ultimately linking it to the patient’s safety.
• Immediate actions may be taken to rectify the problem wherever applicable.
• Appropriate CAPAs can be initiated based on the findings of the investigation and risk assessment.
• Site QA must implement the CAPA and monitor its effectiveness.
• Site Quality Assurance can assess whether the complaint is substantiated or non-substantiated and its impact on the marketed product.
• Substantiated complaints can be categorized as Critical/Major/Minor based on the investigation findings by the site Quality Assurance Head/Designate.
• The investigation must be completed within thirty (30) calendar days from the complaint awareness date.
• If an investigation is incomplete within thirty (30) calendar days, an interim report must be prepared within the original due date and an extension can be taken with justification.
• After completion of the investigation, the final investigation report must be prepared and shared with the complainant.
• Site Quality Assurance can initiate product recall, if applicable, based on the decision of the recall committee as per the recall procedure.
• Site Quality Assurance Head must notify Corporate Quality Head, all stake holders and management about the recall.

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Receipt and handling of samples

• Complaint samples must be photographed for depicting the nature of the complaint and labeled as “Complaint Sample” by site QA. The photographs must be attached along with the market complaint documents for future reference.
• Three attempts can be made by site QA to collect the complaint sample and additional information for investigation if not received.
• The investigation must be initiated based on available information. If the complaint sample is not available or submitted post-follow-up within the timeline, the complaint can be closed. However, if the complaint sample is received after the closure of the complaint, the same must be re-opened.
• The procedure of investigation and sharing information with stakeholders can be as per the procedure mentioned earlier.
• All complaints received must be stored as per the prescribed conditions in the designated area till the closure
  of market complaints. Complaint samples may be retained for training purposes.
• Site Quality Assurance Head/Designate can ensure the destruction of complaint sample after closure
  of the complaint.

Closure of complaint

• The complaint must be closed by site QA within sixty (60) calendar days from the complaint awareness date
  which includes the time period of thirty (30) calendar days for investigation.
• In the case where the investigation is extended beyond thirty (30) calendar days, the complaint can be closed after thirty (30) calendar days from the date of completion of the investigation.
• Site QA must ensure the initiation of action items for CAPA before the closure of the complaint.
• Site QA can maintain the complaint records along with investigation records.

Trending of complaints

• Trend analysis must be performed by Site Quality Assurance as per the following steps:
  — Identification of trending need
  — Trending frequency
  — Data collection and presentation
  — Data verification
  — Data Analysis
  — Data evaluation and interpretation
• Trend analysis for product complaints must be based on product, dosage form, market, nature of the complaint, categorization of complaint (initial and final category), substantiated/non-substantiated complaint, the status of complaint (open/close), root cause, etc.
• Trend analysis for ADE complaints must be based on product, dosage form, market, and category (seriousness and expectedness criteria).
• The frequency for trend analysis can be quarterly and annual.
• Trend analysis can be completed within one month of the completion of the quarter/year. Rolling data must
  be considered for trending.
• Trending data can be collected as per applicable QMS.
• Collected data must be compiled and presented by site Quality Assurance.
• Data can be verified by a cross-functional team.
• The collected data must be analyzed by statistical/logical methods using appropriate tools like pie charts, bar charts, Pareto analysis, etc.
• Trending can identify KPIs that help in the reduction or elimination of specific and repetitive defects.
• Trending can identify areas of improvement where there is any recurrence of problems. Appropriate
• CAPAs can be initiated accordingly. The impact of trend analysis must be considered for an impact assessment on other products/batches.
• A summary report for trend analysis can be prepared by site QA and reviewed by the cross-functional
  teams and approved by the site Quality Assurance Head.

Management Reviews

• Site Quality Assurance must communicate the summary of market complaint information to management for review. The frequency of communication can be as per company policy.

Record Keeping

• Market Complaint Records must be maintained for a period of ten (10) calendar years for manual records for electronic records, the normal retention period adopted by the company can be followed.

Quality Metrics Data

• FDA Safety and Innovation Act (FDASIA),2012, authorized the collection of manufacturing quality data from pharmaceutical companies and also obtaining certain records from drug manufacturers in lieu of, or in advance of, an inspection.
• FDA is considering the utilization of quality metrics as an input to its inspection models as well as to predict possible drug shortages, determine inspection schedules for a manufacturer, assess post-market change reporting, and restructure the format of inspection.

Some of the metrics on which the FDA can be considered:

Product Quality Complaint Rate (PQCR):

These are complaints involving any possible, including actual, failure of a drug to meet any of its specifications designed to ensure that any drug conforms to appropriate standards of identity strength, quality, and purity.

This does not include a lack of effect. This can be calculated as follows:

Product Quality Complaint Rate (PQCR) = the number of product quality complaints received for the product divided by the total number of dosage units distributed in the current reporting timeframe.

As per the ISPE Quality metrics initiative, quality metrics pilot program wave 2, the following calculations can help in analysis.

1. Total Complaint Rate per million packs excluding lack of effect = Total complaints excluding Divided by Total number of packs Divided by 106 for a site.
2. Critical Complaint Rate per million packs = The number of critical complaints (based on final investigation classification) Divided by the Total number of packs produced per site Divided by 106 Explanation
   Substantiated and Confirmed Complaints Consider those complaints for which final categorizations are assigned. Consider only confirmed & substantiated complaints.

Total No. of complaints

• All complaints received on the site irrespective of their categorization.
• The above two do not include ADE.
• Total No. of FG lots approved
• Total No. of Finished Goods for which QA has taken the decision to release the lots.
• Total number of FG + Salable Intermediate lots Dispatched
• A total number of Finished API and Saleable Intermediate dispatched to customers by the manufacturer.

Annexure 1: Trending of market complaints

• Frequency of citation of market complaint (YYYY)
• Reporting adverse drug experiences to FDA
• Complaint handling procedure
• Procedures to be written and followed
• Items to cover on annual reviews
• A written record of complaint to include findings, follow-up
• Complaint investigation/follow-up findings
• Adverse drug experience
• Quality control review
• Complaints reviewed by the quality control unit
• Review of problem drugs
• Maintenance of complaint file
• Reason for not conducting a complaint investigation
• Written complaint record to be maintained at the facility

Market complaints related to dosage forms (YYYY)

• API
• OSD
• Parenteral
• Other

Market complaints related to nature (YYYY)
Bacteriological contamination
ADR
Colored vials
Higher thickness and weight
Dissolution
Colored/stain material
Empty container
Foreign matter
Impurity
Incorrect barcode
Lack of effectiveness
Leakage
Metal particle
Missing pills or tablets
Mixup
Short count
Overfill and underfill
Sticking of capsules
Vial stopper

Market complaints related to API (YYYY)

• Colored stain material
• Foreign matter
• Impurity

Market complaints related to OSD manufacturing

• ADR
• Overfill and underfill
• Missing pills or tablets
• Lack of effectiveness
• Dissolution
• Empty container
• Higher-thickness and higher-weight tablets
• Sticking of capsules

Market complaints related to parenteral manufacturing

• Appearance
• Bacteriological contamination
• Colored vials
• Empty container
• Foreign matter
• Metal particle
• Leakage
• Vial stopper

Risk assessment

• The criteria for initial and final classification of complaints into critical, non-critical, major, and minor categories are, to some extent, subjective, and may vary across different pharma companies.
• The decision to raise FAR and/or initiate product recall is evaluated on a case-by-case basis given the lack of a standard industry approach towards categorizing complaints for which FAR needs to be initiated.
• There were many cases where failing to initiate FAR/recall led to regulatory observations.

Introduction

• Risk assessment is an approach to standardize the process of complaint classification (into critical/major/minor categories) which helps to arrive at a logical conclusion on the need to raise FAR or initiate product recall.
• It is based on the concept of assessing important aspects of ‘substantiated market complaints’ – the severity of the complaint, frequency of occurrence, and detectability of defect – in order to bucket the complaint into a pre-defined category and subsequently evaluate the need for raising FAR/product recall.

Pre-requisites

• Checklists, prepared as per dosage forms, mapping the usual kind of defects/complaints most commonly observed in a particular dosage form and the severity of implication of the respective defect (bucketed into critical/major/minor).
• Database of previous ‘substantiated’ market complaints classified by date of receipt of the complaint, product, dosage form, and action taken to address the complaint.

• Methodology

• At the time of receipt of the complaint, all the required information including source, description of defect observed, etc. is captured in the query template.
• This information forms the basis of the initial classification of complaints into critical and non-critical categories on the basis of information available at hand and the implication of observed defects on
  patient safety and product efficacy.
• Initial classification as Critical and Non-Critical can be performed on a qualitative basis considering the severity of the complaint and its occurrence.
• The occurrence of complaints must be captured for the particular batch in terms of the dosage unit.
• The occurrence of a complaint received without batch number must also be captured in terms of the dosage unit.
• Severity and occurrence can be assessed as per the description given in the subsequent respective part
  of the scoring methodology.
• On completion of the initial classification, all the critical complaints must be evaluated whether there is a
  need to raise FAR or not.
• For other non-critical complaints, decisions regarding of FAR can be taken based on the repeatability of
  the defect.

Definitions

• Risk Assessment: A systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards.
• Risk Analysis: Estimation of the risk associated with the identified hazards.
• Risk Evaluation: Comparison of the estimated risk against given risk criteria using a quantitative or qualitative scale to determine the significance of the risk.
• Severity: A measure of the possible consequences of a hazard.
• Occurrence: Identification of the repetitive nature of the hazard.
• Detectability: The ability to discover or determine the existence, presence, or occurrence of a hazard.

Cephalosporins Drugs