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.

Medical Device Record - Part I

Due to the length of this topic, this blog is divided into two sections, I and II.

1)    Basically, Device Master Record (DMR) is a catalog and compilation of device-specific documentation required for the procurement of materials and components, manufacture, and evaluation of the device. DMR is also a compilation of current records and the status of the physical and software  configuration of the device.

A unique DMR is established for each type or model (family) of medical device manufactured by the company.

2)    Types of Documents included in DMR 

For each type or model of medical device, the DMR includes the following types of documents. However, not all types of documents specified in this section are totally relevant for each type or model of device. For a particular device, the individuals responsible for Engineering, Production, Regulatory and QA decide jointly which specific documents are to be included in the DMR.

Note: all these documents should be in the final form, initialed and dated by responsible parties. Each document must have a unique identification for traceability.

2.1.    Device Specifications shall include, but not limited to the
     following:

§  Trade and Common names of the Device;

§  Intended Use/Uses of the Device;

§  Performance Characteristics and Theory of Operation of the Device;

§  Physical Characteristics of the Device like size and weight;

§  Environmental Limitations of the Product;

§  Product Stability of the Product;

§  Storage Requirements like temperature and humidity;

§  User Safety Characteristics;

§  Component, Subassembly and Assembly Drawings and Specifications;

§  Bills of Materials (BOM); BOM must be detail and organized properly;

§  Compositions and Formulations; What type of materials;

§  Wiring, Piping, Electronic and Engineering Drawings;

§  All Related Software Information.

2.2     Manufacturing Process Specifications: This is mainly to
          show how this product is being made, examples are shown
          below:

§  Process Flow Charts, Manufacturing Site and its Flow;

§  Process/assembly Lines Diagrams;

§  Manufacturing Instruction of the Products:

§  Equipment, Tools and Molds requirement to make this product;

§  Manufacturing Environment Specifications such as cleanroom specification;

§  Setup procedures for equipment, tool and molds;

§  Operator Instructions;

§  Equipment Maintenance procedures like preventive maintenance and its schedule.

§  Validation reports for special processes like IQ/OQ/PQ of processes.

§  Sterilization specifications, procedures, and validation reports like Gamma, ETO or E-beam sterilization.

§  Blank work orders, nonconforming product/process forms, and other reporting forms.

2.3     Quality Assurance Procedures and Specifications:

·       Quality System Manual both Hardcopy and Softcopy;

·       Quality System Operational Procedures. There should have many procedures for this operation.

·       Quality System Forms like forms for CAPA and non-conforming products.

·       Process Control Specifications/Charts;

·       Control Plans, Instructions and Acceptance Criteria for Incoming, in-process, and finished device inspection and testing;

·       Procedures and Acceptance Criteria for the Verification of Packaging, Labeling, Installation, and Servicing Activities;

·       Blank Work Order forms for Recording Inspection/testing activities, traceability, and other data for device history records;

·       Device Release Review/evaluation checklists.

2.4     Packaging and Labeling Specifications of Device:

§  Package Drawings and Specifications;

§  Filling/Packaging procedures;

§  Label/Labeling drawings;

§  Instruction or direction for use manuals. This must be the latest and shall be updated as new information becomes available.

2.5     Installation, Maintenance, Training and Servicing
         Specifications:

§  Installation, Specifications and Instructions for the Device;

§  Maintenance Instructions for the device;

§  Servicing Specifications and Manuals.

§  Training Documents.

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.

Design Transfer

Design transfer is another critical phase of the design control of the medical device.  This is the phase of transferring the design into manufacturing or production. The key is to ensure the production specifications are being done right. This is to ensure that the manufactured devices can be repeatedly and reliably produced within product and process capabilities.

Therefore, to achieve that, it is critical to have frequent consultation and intensive interaction especially between design engineering and production engineering.

All must be involved with design review meetings and activities from the beginning to end. Intensive interaction is especially required when the device is new to the production team.

Some examples of production specification are as below:

                  

                  ·       Assembly Drawings

·       Component Procurement Specification

·       Computer-aided Manufacturing (CAM) Programming Files

·       Digital Data Files

·       Inspection and Test Specification

·       Manufacturing Instructions

·       Manufacturing Jigs and Aids

·       Master EPROM

·       Programmable Device Files

·       Prototypes

·       Training Materials

·       Workmanship Standards

Another key element is having a design and development procedure which include a qualification assessment for the completeness and adequacy of the production specifications.

Secondly, the procedures shall ensure all documents and articles regarding production specifications are reviewed and approved by respective team members.

Thirdly, procedures should also ensure that only approved specifications are used in the manufacturing of the medical devices.

I found that it is very useful to have all the documents about production specification into a formal ‘design transfer’ template. This template must contains all the final version of all documents of the design transfer.

 But, unfortunately, I had encountered many medical device manufacturers failed to have a seamless design transfer. For example, design engineering waited until the last minute to transfer to production and expect the medical devices to be produced perfectly. Therefore, it is critical that the manufacturing and production department not to get involved at the last minute.  You just cannot dump the whole design transfer documentation to the production team last minute.                                                                                                                                                                                                                                         

Reference	Criteria
21 CFR 820.30(h)	Each manufacturer shall establish and maintain procedures to ensure that the device design is correctly translated into production specifications.

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 Validation

The blog is about design validation to ensure the medical device satisfies defined user needs and intended use or uses. Design validation should be performed on initial production units and under simulated or actual conditions in which the medical device will be used.

Design Project Plan should include planning and scheduling of design validation activities. All planned validation activities must be completed with satisfactory result prior to any device can be delivered to the customers.

Designs are validated according to approved and documented protocols. Project manager should be responsible to establish detail of validation protocols. Validation protocols should specify:

·       Acceptance criteria;

·       Clinical Evaluation;

·       Evaluation of Performance of Medical Device;

·       Operating environment and/or conditions;

·       Modes of use;

·       Testing methods, setup and procedure.

                 

Examples of Design Validation activities for medical devices may include the following:

·       Animal testing.

·       Bench testing.

·       Clinical method evaluations in clinical and nonclinical settings.

·       Clinical studies for product to be marketed in the US that approved by IRB and IDE, or by IRB’s only for non-significant risk devices.

·       Clinical studies for product to be marketed in the EU that approved by Ethics Committees and submitted to Competent Authorities.

·       Literature searches on related medical device.

·       Software Validation to include software validation protocol.

·       User acceptance testing.

·       Review of labels and labeling, packaging, and other historical product information.

·       510(k) or PMA historical database searches.

All design validation activities are always documented in design validation reports. For example, forms, report etc for recording data and reporting results are included in design validation protocols. All design validation records include the date when the validation was carried out and the name of the individual(s) or the third party organization like Contract Research Organization (CRO) performing the validation.

During design validation, when the device does not meet requirements and the design must be modified or corrected, the necessary actions required to correct the problem are documented and their implementation is recorded. This may be in minutes of design reviews, memo, in validation reports and studies, or as notes or mark-ups made directly on design output documents.

Sample of design validation records are:

·       Validation methods and protocols with validation results,

·       Actions necessary to address problems, and their associated reports,

·       Identification of individual(s) or CRO and dates performing validation,

·       Software validation method, protocols and results like reports with a lot of screen shots.

·       All protocols and reports must have their respective unique identities to avoid confusing later.

Irrespective of their nature and format, all design validation records include the date, name of the individual(s) performing the validation, records identity number, actual validation report, memo etc are maintained in the Design History File (DHF).

Reference	Criteria
21 CFR 820.30(g)	Does the company establish and maintain procedures for validating the device design?
21 CFR 820.30(g)	Is design validation performed under defined operating conditions on initial production units, lots, or batches, or their equivalents?
21 CFR 820.30(g)	Does design validation ensure that devices conform to defined user needs and intended uses and include testing of production units under actual or simulated use condition?
21 CFR 820.30(g)	Does design validation include software validation and risk analysis, where appropriate?
21 CFR 820.30(g)	Are results of the design validation, including identification of the design, method(s), the date, and the individual(s) performing the validation, documented in the DHF?

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.