Storage and Distribution Part I

This blog talks about storage and distribution portion of the medical device. The storage and distribution areas had to be managed carefully and systematically with proper documentation. A great Enterprise Computer system will help.

1) Storage Areas

1.1 There should be two separate storage areas, one for the materials which make the medical device and the other area is specifically for finished product stockroom. In addition, there should be holding and quarantine areas in the production areas which are used for the receiving, shipping, inspection, material staging, in-process products, nonconforming materials and products, tooling, small equipment, supplies, etc.

For example, quarantine areas are important to ensure no out of specification raw materials being used to make the medical device and finished products being sent to customers.

1.2 The production and engineering groups are responsible for operating the storage, receiving and shipping areas, as well as various storages and holding areas on the production floor. It is prudent to organize the product floor to be logical and sequential. Normally, Quality Assurance is responsible for nonconforming product holding and quarantine areas.

1.3 Storage and holding areas are always maintained in good condition to prevent damage or deterioration of stored products. You do not want any of the products exposed to undue rain, humidity or insect infestation to be destroyed and damaged causing a lot of money. Product return or recall can be costly as well.

All products in storage are identified and arranged in groups according to their type. When product deteriorates or expired over time the stock is rotated; i.e., oldest deliveries are used first (“first-in-first-out” or FIFO system). For example, if the medical device in question has an expiration period of two years, you need to ensure the product with the shortest expiration date to be sold first rather than the other way around.

2) Inventory Management System

2.1 Material and finished product warehouses are controlled using an inventory management system. In this day and age, there are many such inventory management system out there. The inventory management system also controls the in and out movement of all stock materials used in production and all finished products shipped to customers.

2.2 Materials and parts are entered into the system with their part number, serial number, description, quantity, location in the warehouse, and purchase order number or job number when applicable. For products with limited shelf life the product expiration date is also recorded and to be sold first.

2.3 The inventory management system can report available in-stock quantities and turn-over times. The system is used to minimize inventory levels, optimize turn-over time, and assure stock rotation. This system can be deployed as a way to manage production more efficiently.

2.4 Once every six months or any other period deem appropriate, the warehouses are inventoried and the stock count is reconciled with the inventory management system. In many large medical device company, millions worth of products are missing and unaccounted for due to theft, misplacement or other reasons.

3) Assessment of Stock

3.1 Every six months or so, storage areas are inspected and cleaned. The stock is assessed for damaged or deteriorated products. Identification of products is checked. A product nonconformity report is issued when damaged, deteriorated, or unidentified products are found. Inventory levels of stock are also checked. The Production Supervisor records results of the assessment. This is a time to use a suitable computer system.

4) Receipt and Dispatch Authorization

4.1 Products are authorized to be received to, and dispatched from, various storage, holding and quarantine areas only when they have appropriate production and acceptance status. The QA or QC persons who determines and identifies the production and acceptance status of a product implicitly gives the authorization with objective evidence.

4.2 Only products that have passed receiving inspection are authorized to be placed in, or dispatched from, the material warehouse and the material staging areas in production. They must be objective evidence of the products or parts passing the inspection.

4.3 Only products that have passed specified in-process inspections are authorized to be released from inspection holding areas and be moved to the next processing stage.

4.4 Only products that have passed the final acceptance inspection are authorized to be received in the finished product storage, or be moved to the shipping area and dispatched to customers. Perhaps, it is a good idea to have a system like the QC manager need to sign them off in every stage to prevent potential problems.

4.5 Nonconforming products with unknown inspection status are not authorized to be received in the material warehouse, staged for production, or dispatched to subcontractors or customers. Products with such negative or unknown acceptance status are placed in appropriate quarantine or holding areas and locations. When such nonconforming products are found and they must be quarantined VERY qucikly and must be marked conspicuously.

Reference	Criteria
820.130	Does the company ensure that device packaging and shipping containers are designed and constructed to protect the device from alteration or damage during the customary conditions of processing, storage, handling, and distribution?
820.140	Has the company established and maintained procedures to ensure that mix-ups, damage, deterioration, contamination, or other adverse effects to product do not occur during handling?
820.150 (a)	Has the company established and maintained procedures for the control of storage areas and stock rooms for product to prevent mix-ups, damage, deterioration, contamination, or other adverse effects pending use or distribution?
820.150 (a)	Has the company established and maintained procedures to ensure that no obsolete, rejected, or deteriorated product is used or distributed?
820.150 (a)	For product that deteriorates or becomes obsolete over time, is product stored in a manner to facilitate proper stock rotation, and is the condition assessed as appropriate?
820.150 (b)	Has the company established and maintained procedures that describe the methods for authorizing receipt from and dispatch to storage areas and stock rooms?
820.160 (a)	Has the company established and maintained procedures for control and distribution of finished devices to ensure that only those devices approved for release are distributed?
820.160 (a)	Has the company established and maintained procedures to ensure that purchase orders are reviewed to ensure that ambiguities and errors are resolved before devices are released for distribution?
820.160 (a)	Where a device's fitness for use or quality deteriorates over time, do the procedures ensure that expired devices or devices deteriorated beyond acceptable fitness for use are not distributed?
820.160 (b)	Does the company maintain distribution records that include or refer to the location of appropriate information?

Disclaimer: Although the author had exhaustively researched all sources to ensure the accuracy and completeness of the information contained in this blog, but no warranty and fitness is implied. I assumed no responsibility and implied warranty of any kind for errors, inaccuracies, omission, or any inconsistency herein. No liability is assumed for incidental or consequential damages in connection with the use of the information contained herein. Readers should always use their own judgment and review all related regulatory guidelines. Guidelines can change over time.

Labeling and Packaging Part II

Product packaging and labeling must be treated as an integral part of the medical device itself. Therefore, the product is not completed and could never be released for distribution before it is packaged and all specified labeling and packaging requirements of the quality management system fulfilled. For example products manufacturing must also apply to labeling and packaging as well. 

Therefore, any operational procedures and other quality system documentation related to packaging and labeling must be followed, examples are shown below:

1) Design control, including design validation and control of design output and changes for labeling and packaging;

2) Control of packaging and labeling processes including personnel training,

process validation, work instructions, process monitoring, and process records;

3) Inspection and final acceptance of packaging and labeling; and

4) Establishment and maintenance of necessary records for labeling and packaging.

The following talks about labeling and packaging design and validation. Labeling and packaging design and validation must also be carried out like it is an integral part of the product. 

1) Labeling and packaging, and their artwork, are developed in the phase of product design as in any part of the medical device itself. The development processes are implemented in accordance with Operational Procedure for Design Control, to include requirements for design input, design planning, documenting and controlling design output, conducting design reviews, and verifying and validating the labeling and packaging design.

2 ) For example, medical device products to be marketed in the European Union and South Korea, labeling and instructions for use are translated into foreign national languages versions according to the intended plan for placing the product on the respective market. The translation process and the correctness of the translations is undertaken according to the procedures. For examples, translation must be done by qualified translators.

3) When packaging is designed to meet certain performance requirements, such as sealing the product to protect it from heat, light or contaminants; or structural ability to withstand stacking or shipping loads, the packaging is validated by testing it under actual or simulated conditions of distribution, storage and use. For example, when the medical device is intended to be marketed in a region with high temperature and humidity. The product packaging must be validated again humidity and relative humidity.

4) Packaging for sterile products is likewise validated to test packaging materials and the seal. There are many types of sterilization techniques such as Wet/steam sterilization, Dry heat sterilization, Ethylene oxide, Sporicidal chemicals, Glass Plasma and Irradiation (Gamma rays).

 

5) Labeling integrity is validated to ensure that labels will remain in place and be legible under normal operating and use conditions. There are many requirements for label like what symbols to use, what font size to use and manufacturing site and expiry are some examples of key information printed on the labels.

Reference	Criteria
820.12	Has the company established and maintained procedures to control labeling activities?
820.120 (a)	Are labels printed and applied so as to remain legible and affixed during the customary conditions of processing, storage, handling, distribution, and use?
820.120 (b)	Has it been established that labeling is not released for storage or use until a designated individual has examined the labeling for accuracy?
820.120 (b)	Is the release of labeling, including the date and signature of individuals performing the examination, documented in the device history record (DHR)?
820.120 (c)	Has the company stored labeling in a manner that provides proper identification and is designed to prevent mix-ups?
820.120 (d)	Does the company control labeling and packaging operations to prevent labeling mix-ups?
820.120 (d)	Are the label and labeling used for each production unit, lot, or batch documented in the device history record (DHR)?
820.120 (e)	For devices where a control number is required by product traceability requirements, is that control number on or does it accompany the device through distribution?

Labeling and Packaging Part I

Product packaging and labeling must be treated as an integral part of the medical device itself. Therefore, the product is not completed and could never be released for distribution before it is packaged and all specified labeling and packaging requirements of the quality management system fulfilled. For example products manufacturing must also apply to labeling and packaging as well.

Therefore, any operational procedures and other quality system documentation related to packaging and labeling must be followed, examples are shown below:

• Design control, including design validation and control of design output and changes for labeling and packaging;

• Control of packaging and labeling processes including personnel training, process validation, work instructions, process monitoring, and process records;

• Inspection and final acceptance of packaging and labeling; and 

• Establishment and maintenance of necessary records for labeling and packaging.

The following talks about labeling and packaging design and validation. Labeling and packaging design and validation must also be carried out like it is an integral part of the product.

1) Labeling and packaging, and their artwork, are developed in the phase of product design as in any part of the medical device itself. The development processes are implemented in accordance with Operational Procedure for Design Control, to include requirements for design input, design planning, documenting and controlling design output, conducting design reviews, and verifying and validating the labeling and packaging design.

2 ) For example, medical device products to be marketed in the European Union and South Korea, labeling and instructions for use are translated into foreign national languages versions according to the intended plan for placing the product on the respective market. The translation process and the correctness of the translations is undertaken according to the procedures. For examples, translation must be done by qualified translators.

3)  When packaging is designed to meet certain performance requirements, such as sealing the product to protect it from heat, light or contaminants; or structural ability to withstand stacking or shipping loads, the packaging is validated by testing it under actual or simulated conditions of distribution, storage and use. For example, when the medical device is intended to be marketed in a region with high temperature and humidity. The product packaging must be validated again humidity and relative humidity.  

4  )Packaging for sterile products is likewise validated to test packaging materials and the seal. There are many types of sterilization techniques such as Wet/steam sterilization, Dry heat sterilization, Ethylene oxide, Sporicidal chemicals, Glass Plasma and Irradiation (Gamma rays). 

 

5) Labeling integrity is validated to ensure that labels will remain in place and be legible under normal operating and use conditions. There are many requirements for label like what symbols to use, what font size to use and manufacturing site and expiry are some examples of key information printed on the labels.

Reference	Criteria
820.12	Has the company established and maintained procedures to control labeling activities?
820.120 (a)	Are labels printed and applied so as to remain legible and affixed during the customary conditions of processing, storage, handling, distribution, and use?
820.120 (b)	Has it been established that labeling is not released for storage or use until a designated individual has examined the labeling for accuracy?
820.120 (b)	Is the release of labeling, including the date and signature of individuals performing the examination, documented in the device history record (DHR)?
820.120 (c)	Has the company stored labeling in a manner that provides proper identification and is designed to prevent mix-ups?
820.120 (d)	Does the company control labeling and packaging operations to prevent labeling mix-ups?
820.120 (d)	Are the label and labeling used for each production unit, lot, or batch documented in the device history record (DHR)?
820.120 (e)	For devices where a control number is required by product traceability requirements, is that control number on or does it accompany the device through distribution?

Disclaimer: Although the author had exhaustively researched all sources to ensure the accuracy and completeness of the information contained in this blog, but no warranty and fitness is implied. I assumed no responsibility and implied warranty of any kind for errors, inaccuracies, omission, or any inconsistency herein. No liability is assumed for incidental or consequential damages in connection with the use of the information contained herein. Readers should always use their own judgment and review all related regulatory guidelines. Guidelines can change over time.

Design Changes

Design changes for a medical device is very common due to many reasons such as a replacement with a better and cheaper components or to comply with a new regulatory guideline. 

 

For example to comply with Restriction of Hazardous Substances (RoHS) also known as Directive 2002/95/EC and it was originated from European Union to restricts the use of six hazardous materials found in electrical and electronic products. All applicable medical device in the after July 1, 2006 must pass RoHS compliance. 

 

Therefore, medical device companies may have many design changes to comply with RoHS in order to market the product in the EU. This may be a major design change involving many components depending on the complexity of the medical device in question.

 

In general, there are two types of design changes, the first is during design process of the device and the second is changes after the device had been released. 

 

During the design process, for example, before design output documents are transferred to production, design changes are controlled internally within the Design Engineering group and other per company protocol. 

 

In this phase the project manager of the developmental product has the authority to approve all changes. The manner in which the request for change, its review, and change authorization are documented depends on the nature of the change and how early or late in the design cycle the change is done. 

 

Typically, these changes are documented as notes on design documents such as:

• Drawings
• Specifications,
• Calculations,
• Minutes of design review meetings

However, after the design is released to regulators for pre-market approval, is undergoing clinical trials, or is released to production, it will be a lot more involvement of many departments like regulatory affairs, engineering, marketing and validation group etc. 

 

The changed device many need to have to be partially validated again or the engineering group many need to perform risk analysis and update the risk managemet file. 

 

The sponsor should also comply with Engineering Change Request, Control of Documents and regulatory affairs protocol. For example, after the product is deemed RoHS, the label should have a sticker of RoHS added to that effect.

Reference	Criteria
21 CFR 820.30(i)	Each manufacturer shall establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation.

Disclaimer: Although the author had exhaustively researched all sources to ensure the accuracy and completeness of the information contained in this blog, but no warranty and fitness is implied. I assumed no responsibility and implied warranty of any kind for errors, inaccuracies, omission, or any inconsistency herein. No liability is assumed for incidental or consequential damages in connection with the use of the information contained herein. Readers should always use their own judgment and review all related regulatory guidelines. Guidelines can change over time.

Device Master Record- Part II

This is the second section of the blog on Device Master Record (DMR). This blog talks about format of DMR index and the review, approval and change control of documents.

            1) Format of the DMR Index

DMR is maintained on the company computer network in a Microsoft Word table, Excel or equivalent format. The model of the DMR table should have a formal index form as well entitled Device Master Record Index.

Individual documents referenced in the DMR Index are identified by:

• Document Number,
• Title (or description),
• Category and document type (drawing, bill of materials, procedure,
  work instruction, etc.)
• issuing authority like department; engineering, regulatory affirs etc.

         The effective date, revision level, and distribution of a document included in the
         DMR, the DMR Index should be cross-referenced with the appropriate Document  
         Control Master List, where the document status information is maintained to avoid
         confusion.

          2) Review, approval and changes

The initial DMR Index, and any subsequent addition or deletion of documents form the index, are to be reviewed and approved by the individual responsible for Quality Assurance plus other departments. 

The review and approval of the DMR Index is to ensure the completeness and relevance of the DMR index, rather than for the correctness of the individual DMR documents. The individual documents in the index should have been independently reviewed and approved by their issuing authority, in accordance with the procedure entitled in “Control of Documents”.

DMR review, approval, change control, distribution control, retention of obsolete copies, and other document control requirements are the same as apply generally to controlled documents, as specified in Procedure “Control of Documents”.

This DMR index must be treated with seriously and any update must be performed expeditiously to reflex other related changes. For example, if there is a change in the bill of material and it is not updated quickly in the index, the purchasing department may buy the wrong components.

Reference	Criteria
21 CFR 820.181	Has the company maintained device master records (DMR’s)?
21 CFR 820.181	Has the company ensured that each DMR is prepared and approved in accordance with Document Control requirements?
21 CFR 820.181 (a)	Does the DMR for each type of device include, or refer to the location of, device specifications including appropriate drawings, component specifications, and software specifications?
21 CFR 820.181 (b)	Does the DMR for each type of device include, or refer to the location of, production process specifications including the appropriate equipment specifications, production methods, production procedures, and production environment specifications?
21 CFR 820.181 (c)	Does the DMR for each type of device include, or refer to the location of, quality assurance procedures and specifications including acceptance criteria and the quality assurance equipment to be used?
21 CFR 820.181 (d)	Does the DMR for each type of device include, or refer to the location of, packaging and labeling specifications, including methods and processes used?
21 CFR 820.181 (e)	Does the DMR for each type of device include, or refer to the location of, device specifications including appropriate drawings, component specifications, and software specifications, and installation, maintenance and servicing procedures and methods?

Disclaimer: Although the author had exhaustively researched all sources to ensure the accuracy and completeness of the information contained in this blog, but no warranty and fitness is implied. I assumed no responsibility and implied warranty of any kind for errors, inaccuracies, omission, or any inconsistency herein. No liability is assumed for incidental or consequential damages in connection with the use of the information contained herein. Readers should always use their own judgment and review all related regulatory guidelines. Guidelines can change over time.