Product Defects

Recall Procedure

Recall, Purpose :

Recall, To ensure recall of products that are known or suspected to be defective or hazardous in accordance with a pre-determined plan promptly and effectively from the market

Recall, Scope :

This procedure is applicable for all products manufactured and distributed from XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Recall: A process for withdrawing or removing a pharmaceutical product from the pharmaceutical distribution chain because of defects in the product, complaints of serious adverse reactions to the product and/ or concerns that the product is or may be counterfeit. The recall might be initiated by the manufacturer, wholesale dealer, license holder, or Department of Health.
[][]Market Withdrawal: Market Withdrawal means a firm’s removal or correction of a distributed product which involves a minor violation that would not be subjected to legal action by the Drugs Administration or which involves no violation, e.g., normal stock rotation practices, routine equipment adjustments and repairs etc.
[][]PMD: Product Management Department
[][]QA: Quality Assurance

Responsibilities:

The roles and responsibility is as follows:

Head of PMD

[][]Responsible for determining the intensity of recall to be taken by consultation with Head of QA and taking necessary action.
[][]When product is distributed in domestic/ overseas market, Head of PMD or his authorized nominee shall inform Head of QA for the action to be taken for recall.
[][]Coordinate the recall after obtaining approval from Managing Director.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Classification of Recall:

[][]Recalls are classified according to the following system
Class I recalls: Occur when products are potentially life-threatening or could cause a serious risk to health.

Examples of Class I Defects

[][]Wrong Product (label and contents are different products)
[][]Correct product but wrong strength, with serious medical consequences
[][]Microbial contamination of sterile injection or ophthalmic product
[][]Chemical contamination with serious medical consequences
[][]Mix up of some products (‘rogues’) with more than one container involved.
[][]Wrong active ingredient in a multi-component product with serious medical consequences

Class II recalls: Occur when product defects could cause illness or mistreatment, but are not Class I.

Examples of Class II Defects

[][]Mislabeling e.g. wrong or missing text or figures
[][]Missing or incorrect information- leaflets or inserts
[][]Microbial contamination of non-injectable, non-ophthalmic sterile product with medical consequences
[][]Chemical/ physical contamination (significant impurities, cross contamination, particulates)
[][]Mix up of products in containers (“rogues”)
[][]Non-Assurance with specification (e.g. assay, stability, fill/ weight or dissolution)
[][]Insecure closure with serious medical consequences (e.g. cytotoxics, child resistant containers, potent products)
Class III recalls: occur when product defects may not pose a significant hazard to health, but withdraw may be initiated for other reasons.

Examples of Class III Defects

[][]Faulty packaging e.g. wrong or missing batch number or expiry date
[][]Faulty closure
[][]Contamination- microbial spoilage, dirt or detritus, particulate matter
[][]Recall system shall be followed in case of Instructions from Regulatory authorities or Voluntary recall by XX authority.

Reason:

=>Reports of adverse reaction.
=>Non-conforming result of on-going stability study.
=>Formulation problem/ Mix-up/ contamination.
=>Labeling errors.
=>Any other reasons.
[][]Head of Quality Assurance shall advise to carry out proper investigation for confirmation of reported defects either jointly or independently by QC, PD, Production & Quality Assurance. PMD personnel can also participate in investigation.
[][]After confirmation and justification of reported defects, Head of Quality Assurance shall discuss with Head of Production and Head of PMD.
[][]Once it is agreed to recall the product(s), Head of Quality Assurance shall seek permission for it from Managing Director (Annexure-III). A Recall Reference no. shall be given on this form as follows:

PR/XX/001
=>Where, ‘PR’ represents Product Recall.
=>‘XX’ represents the last two digits of the year 20XX
=>‘001’ represents for serial number

Recall Panel:

=>Managing Director (MD)
=>Head of Quality Assurance
=>Head of Production
=>Head of PMD
=>Head of Sales
=>Head of Distribution
=>Head of Quality Assurance shall furnish the batch details for recall notification in Annexure-IV. This shall be then forwarded to Head of PMD and Head of sales.

Recall notification shall include:

=>Products name including brand name, its strength and pack size and other details like,
=>Product License (D.A number) if applicable.
=>Batch or Lot number, Batch size, Mfg. date, Exp. date.
=>Nature of defect and reason.
=>Action to be taken (urgent within time frame/ immediate quarantining of stock /return stock) with labeling instruments & specific precautions.
=>Date of  withdrawal.

[][]The Head of PMD through Distribution shall send a product recall circular, immediately upon receiving the product recall decision, to all concerned persons requesting them to return all stock of the batch under question to the depots and informing them that a credit note for the stocks returned shall be issued to them at the earliest.
[][]All product recall requests shall be given top priority unless otherwise indicated by recall coordinator.
[][]The Head of PMD along with Distribution shall immediately arrange to freeze all stocks of the batch lying with distributors, agents and customers. He shall also instruct the entire sales force to freeze further sales of batch at every distribution, sales point (stockiest, chemists, doctors, hospitals etc). This shall also include goods under transit.

[][]In case of recall as per directives of competent or Regulatory Authorities, the information shall be forwarded to them (To include Regulatory Authorities of other Countries to which the batch has been distributed). The decision of disposal of recalled batch shall be as per their directives and the destruction or disposal shall be done under notification and the Drugs Inspector’s supervision.
[][]Quality Assurance Department will record the receipt, origin & quantity of any recalled product received & holds the recalled product in a secure place to avoid mix up with other materials.
[][]The progress  should be reviewed at regular, frequent intervals to monitor its effectiveness and ultimately to decide that the recall is completed.
[][]Completion will normally be reached when:
=>All the acknowledgement forms issued are returned.
=>The material listed in the acknowledgement forms has been returned.
=>There have been no further returns or further adverse reports concerning the product for a period of 2 weeks.
[][]After thorough investigation, Head of Quality Assurance will issue instructions for safe disposal of the recalled stock in due course and a disposal record will be maintained. An investigation into the root cause analysis of any product defect which led to a recall must be carried out and CAPAs to be prepared to prevent if happing again.
[][]Details of recalls shall be added to the batch dossier for all the batches concerned.
[][]Detailed records of all product returned as part of a recall must be kept.
[][]In case of recall when initiated by company (Voluntarily) this shall be informed to the Regulatory Authority.
[][]In case of voluntary recall, product when received back from market to our depots shall be identified and stored separately in a secured area while awaiting a decision on its disposal. The product shall be written off and destroyed as per the standard procedure.

Documentation:

[][]The decisions, activities and actions including progress of recall shall be documented and duly authorized.
[][]On completion of recall procedure, summary report shall be prepared which shall include the following (Annexure V).
[][]Reason for recall of a product (with Batch No. and other details about the product).
[][]Effectiveness of recall.
[][]Corrective action to prevent reason for recall.
[][]Appropriate training to concern as applicable.

[][]This summary report shall be prepared by Head of Quality Assurance and be circulated to all concerned departments (PD, Production, Accounts, Sales, PMD) and Managing Director.
[][]Distribution records should be readily made available to the person(s) responsible for recall and contain sufficient information of wholesalers, retailers, stockiest and customers/agents for prompt and effective it. (Examples: Addresses, Telephone numbers, inside or outside office working hours, batch number and its quantity with them for both domestic and exported products).

Recall Simulation:

[][]The recall procedure shall be regularly reviewed to ensure that it is up-to-date and shall be simulated ‘in house’ to ensure its effectiveness and familiarity to all key personnel.

[][]The required time limit for simulation exercise (from initiation of  simulation to completion) will be not more than 15 days.

Annexure:

Annexure-I: Product Recall Flowchart
Annexure-II: Product Recall Log Book
Annexure-III: Product Recall Form
Annexure-IV: Recall Notification Form
Annexure-V: Summary Report of Recall

Recall Procedure Read More »

Market Complaint Handling

Market Complaint , Purpose :

Market Complaint , To provide a system for timely response to a product complaint and to make relevant investigation and recommendation with proper documentation.

Market Complaint , Scope :

This procedure is applicable to all types of market complaints received from the market, related to quality, packing and shortage of the products manufactured at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Market Complaint: A written or verbal report originating from customer, retailers, physicians, field supervisor, regional sales coordinator, medical representative, hospitals, regulatory agency and our employees which relates to the inadequacy of the quality, i.e. non Assurance with standards or customer requirements and includes any packaging and labeling requirements, any query regarding specifications, analytical procedure, incomplete text and non conformance with customer requirements should be treated as complaint.
[][]Customer: The person or institution making the complaint.
[][]PMD: Product Management Department.

Responsibilities:

[][]The roles and responsibility is as follows:

Executive/ Manager, PMD

[][]Send the complaints with appropriate details & samples to Manager, Quality Assurance.

Quality Assurance Manager/ designee

[][]Responsible for registering, carrying out the investigation and taking necessary corrective actions, providing necessary technical response to PMD in consultation with General Manager, Plant and Manager, Quality Assurance, generation of the complaint report and closure of the complaint.

Manager, Quality Control

[][]Responsible for carrying out the analysis of samples as per requirement.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Procedure:

Classification of Complaints:

[][]Market complaints to be classified as minor, major and critical.
[][]Minor: Complaints related to physical appearance of packaging of the product.
[][]Major: Complaints related to physical appearance of the products (e.g. broken tablets, fading, spots etc), packaging quantity (e.g. empty blister, empty bottles, empty content etc), label missing, batch printing missing etc.
[][]Critical: Chemical property complaints related to any chemical test failure of a product, e.g. low purity, change in the impurity level and degradation and shall also include the complaints arising due to stability failure. In the event that a batch is considered to be actually or potentially harmful to user, thereby requiring a recall, following relevant SOP.

Raising of Product Complaint:

[][]Any market complaint received or to be raised by PMD / Sales team shall be filled up in the market complaint form (Annexure-III) along with complaint details (Attach original complaint document to this Annexure if applicable). If the details of the complain are not available in the document then the details of the chemist shop or recipient from where the complaint has been received will be recorded in the market complaint form.
[][]Customer complaints which are received by PMD or complaint raised by PMD will be forwarded to Manager, Quality Assurance with appropriate details in the market complaint form (Annexure- III).
[][]Head of Quality Assurance shall send the complaints along with complaint sample, if received, to Manager, Quality Assurance.
Manager, Quality Assurance shall arrange the investigation and generate a comprehensive report on the market complaints investigation form (Annexure–I).

Investigation of complaints:

[][]Manager, Quality Assurance shall record the complaint in a market compliant logbook (Annexure–II). This detail should include a complaint number, name of the product, batch No., Mfg. date, Expiry date, nature of the complaint, name & address of complainant and date of receipt at the investigating site.
[][]Quality Assurance shall assign a distinct control number to every complaint as follows:
MC/XX/001
Where,
MC – Market Complaint.
‘XX’ represents the last two digits of the year 20XX
‘001’ represents for serial number of the market compliant on continuous basis starting from
001 for the calendar year.
[][]If complaint sample is received along with the market complaint, the investigator shall record the quantity of sample received in the market complaint investigation form (Annexure–I).
[][]If no complaint sample is received along with the complaint, the investigator shall record the relevant details disclosed in the complaint form.
[][]Quality Assurance Manager shall carry out the detailed investigation of the market complaint under the supervision of Head of Quality Assurance to find out the root cause of the complaint and to generate corrective & preventive actions. In his/her absence, Head of Quality Assurance shall nominate any other person to carryout activities in this regard.
[][]Investigator shall carefully inspect and record the physical appearance of the sample, seal etc. and compare the details of the references available in documents of the same batch number. Chemical analysis shall be done on the sample at this point of time.
[][]The investigator in consultation with Head of Quality Assurance shall arrange to carry out chemical and / or microbiological analysis of the reference sample (along with the complaint sample, if available). The investigator must also scrutinize the analytical report of the product under reference.
[][]The investigator shall then discuss the results of the analysis with General Manager, Plant for the investigation at production end.
[][]General Manager, Plant along with the respective departmental manager shall investigate the complaint in details.
[][]The investigation should include scrutiny of batch production records for any manufacturing and/or packing problems encountered during the production of the batch.
[][]Any equipment breakdowns recorded during production of the batch and any material quality problems faced during manufacturing and packing of the batch also must be studied.
[][]In case of following nature of the market complaints, AGM, Quality Assurance in consultation with Managing Director may decide to recall the product / batch as per Recall procedure.
[][]Product mix up and label mix up
[][]Failure to meet regulatory specification (i.e. Assay, impurity)
[][]Adverse drug reaction due to product defect.
[][]Contamination due to foreign matter. (e.g. Glass pieces, metal pieces, black particles, particulate matter, microbial growth etc.)

[][]The closure of complaints along with redressal should be completed within 1(one) month period after the receipt of the complaints. Any delays shall be justified.

Product Complaint Redressal:

[][]Head of Strategic Marketing and Communication after consultation with Managing Director shall appraise the customer on the corrective actions taken and on the redressal actions, wherever necessary and a copy of such shall be forwarded to Head of Quality Assurance for his/her reference.
[][]Management Reviews of Complaints:
[][]The product complaint report, the trends, effectiveness of the corrective actions etc. shall be summarized and reviewed in management review meeting.

Annexure:

Annexure-I: Market Complaint Investigation Form
Annexure-II: Market Complaint Log Book
Annexure-III: Market Complaint Form
Annexure-IV: Flow Diagram For Handling of Market Complaints

Market Complaint Handling Read More »

Cross-Contamination prevention during processing in pharma industry

Cross-contamination, Before taking steps regarding Prevention of Cross-Contamination during processing, this is very important to know basic about contamination and Cross-Contamination and what is the basic difference between contamination and Cross-Contamination.

Also Read

Mix Up, Contamination and Cross Contamination in Pharma industry

Cross-contamination

Cross-contamination can be defined as unintentional transfer of chemical contaminants (including allergens), microorganisms, or any other foreign substances from person, food, or object to another person, object or food product.

This problem is generally occurs  at raw food to RTE[ready-to-eat] products, also occurs between allergen free and allegen products.

Cross-contamination products can cause severe food poisoning as harmful bacteria transfer from RTE products which doesn’t subject to any type processing or treatment on not taken any steps to eliminate harmful bacteria from those foods[RTE]. The best example of cross contamination is transfer of bacteria from raw food to cooked food.

Pharmaceutical products are the highest risk of Cross Contamination. Presence of small amount of antibiotics or trace amount of potent drugs cause severe damage to the patients. Carryover of one products residue to another products is consider the highest risk to the patient.

In the recent year, as per UK MHRA[United Kingdom Medicines & Healthcare Products Regulatory Agency], product contamination is the second to third cause to recall products from the market.

Understanding Cross-Contamination

There are several ways to where cross-contamination can occur:

  • Equipment to food
  • Food to food
  • People to food

Equipment to Food

Contamination can be transfer from pantry equipment & utensils to food staff. This type of contamination can be transfer from improper cleaned equipment or utensils to food items and which is not properly sanitized before each use. Here is some example-

  • Using of improper cleaned items such as utensils, slicers, knives, grinder, and juicer to prepare food.
  • Using of cutting and chopping board and use the same knives to cut different food items, such as cutting raw beef and then prepare vegetable salad or RTE food items.
  • Storing RTE [ready-to-eat] food items in an improperly sanitized container, which was previously used for raw food item such as raw beef.

Food to Food

Food can contaminate by bacteria from comes from other foods. This type of cross-contamination seriously dangerous when raw type foods contact with cooked/finished food/RTE Food. Here is some example for of food-to-food cross-contamination-

  • Storing raw chicken in the upper shelf of the refrigerator but cooked chicken store lower shelf of the refrigerator where cooked chicken dripping from raw chicken.
  • Raw meat placed on a on a grill touching another meat that is being cooked.

People to Food

Personnel can be great source of cross-contamination to food items for their inappropriate behavior or lack of training to do the task properly. Here is some points to notify the situation-

  • Handling of food items just using after the toilet without properly personal clean up.
  • Touching Raw Chicken and prepare vegetable salad without properly clean up between the tasks.
  • Handling of apron with wipe hand and subsequently serve foods to individual.
  • Using of towel to clean the kitchen and further use the towel after dry hand.

How to prevent cross-contamination

Production & Related Area

  • All type of line clearance should be perform as per approved SOP and related checklist mentioned on BMR/BPR
  • Avoid similar type of product clearance in same time in side-by-side line.
  • All the system must be properly validated [Equipment/Machine/Facility/System/Process etc.]
  • Before starting of any type of product processing, processing product, list of materials, printing materials, primary packaging materials must be contamination free.
  • Check any type or related starting materials, product residues, products, documents, records, process flow and related documents of the previous products during starting of the new line.
  • Closed system to be introduce for critical products, if possible close system to be introduce for all type of products handling.
  • Campaign production may be the best procedure to achieve satisfactory contamination/cross-contamination free products by following appropriate validated cleaning procedure.
  • During processing, products and direct products contacts part should not be handled with bare hand, use latex free gloves to handle the same with properly spray cleaned with IPA [70% IPA]
  • During production/processing all type of maintenance work must be prohibited and production/processing to be stop during maintenance activities.
  • If any area subject to maintenance activities, to restart of the operation, the area must be properly cleaned and maintenance clearance to be ensure from respective department.
  • Packaging must be properly segregate from processing/filling area, a physical barrier must be introduce to prevent contamination and related operation must be controlled.
  • Product subject to in process control in production area to be confirm that it should not provide the risk for the product and remaining IPC products must be discard and not to add the processed products.
  • Production accessories/stationary/liquid item/ink of image printer/other solvent etc. must be kept in labelled container as per their content present in the defined container.
  • Single line processing to be introduce, never start multiple line/product in the same line
  • Solution container subject to filling should be properly cleaned before using for filling operation especially for aseptic products such as eye drops, which cannot be terminally sterilized due to container criteria [Plastic container].
  • Try to reduce bioburden especially for injectable products and remove outer additional/unnecessary/additional wrapping during delivery at the point of use.

Clothing & Hygiene

  • Appropriate clothing and gowning system to be ensure as per classified area.
  • Clothing should be different for every shit/working hour/every time before entering the processing/filling area.
  • Cleaning agents to be use in proper quantity and agents must be contamination free
  • Clothing and its quality should be appropriate for the process and the grade of the working area.
  • Daily environment monitoring by particle counter machine, air sampling, settle plate count to be carried out as when appropriate.
  • During handling of hazardous material/container/liquid/gas, appropriate PPE[Personnel Protective Equipment] should be ensure.
  • Footwear to be clean properly and each pair of clean shoe to be confirm before entering to the processing/filling area.
  • Lint free non-shedding cloth to be ensure.
  • Minimize the exposure of body surface as less as possible.
  • Repeated wear of same gown in same days must be avoid in processing/filling area.
  • Separate/dedicate PPE to be ensure for beta-lactam and non-beta lactam, other antibiotics, hormone, generic medicine, cytotoxic etc. products.
  • Slippery sandal/shoe/loose shoe etc. to be avoid and appropriate shoe to be use such as lint free clothing shoe to be ensure especially in sterile processing/filling area.
  • Wash the cloth each time before entry of the process room.
  • Washing system to be separate as per designated area.

Utilities and Service

  • Appropriate water to be use in pharmaceutical preparations for its targeted use.
  • Any type of failure regarding water quality test must be notify and action to be taken and production must stop.
  • Chemical and microbial limits and requirements must be made.
  • Validation of the water system to be ensure before using water in pharmaceutical preparations especially First and Second phase must be validate and third phase must be ongoing and report should be made.
  • Water quality must be check before its use.

Steam Quality

  • PQ[Performance qualification] of steam to be ensure.
  • Pure steam and industrial steam to be use as when and where appropriate.
  • Steam must be additive free.
  • Steam must be contamination free and microbial quality must be passed.

Compressed air/Transportation/Cleaning and related activities

  • Air quality to be ensure by passing through appropriate filter.
  • Any sign of spillage/broken/contamination during transport, full quantity must me discard.
  • All type of processed or partially processed, in-process materials, raw materials, partially packed, finished packed should be properly labelled with Product Name, Batch no., Quantity, Packed by, Packing date, Manufacturing date, Expiry date etc.
  • Cleaning solvent/materials use for cleaning, lubrication, pest control should not direct contact to the product and suitable grade of cleaning agent to be ensure.
  • During production, high degree of cleaning and sanitation to be ensure before entering into the processing/production area.
  • Measures must be taken to prevent cross-contamination and its effectiveness to be ensure.
  • Processing/manufacturing area for hormones, penicillin, cephalosporin, generic products, vaccine, antibiotics must be dedicate/segregate to prevent cross-contamination.
  • Transport of Beta lactam and non-Beta lactam antibiotics should not be perform in disclose condition, container must be tightly bind with the appropriate material/stripe. Finished product may be transport with tight pack condition simultaneously.
  • To be clean/clean label should be properly attached on any containers subject to use or unused with product/material name/batch no.

Cross-Contamination prevention during processing in pharma industry Read More »

error: Content is protected by www.pharmaguideline.co.uk !!