Abdul Muheem M.Pharma(Pharmaceutics) Faculty of Pharmacy Jamia Hamdardmuheem.firstname.lastname@example.org
Introduction – Package engineering and Packaging Science, is a broad topic ranging from design conceptualization to product placement. Package design and development are often thought of as an integral part of the new product development process. Quality control of a packaging component starts at the design stage. Packaging is a critical tool in the pharmaceutical industry for product delivery and regulatory compliance, many pharmaceutical companies will do all their packaging within a contamination free environment or Cleanroom. The terms active packaging, intelligent packaging, and smart packaging refer to packaging systems used with foods, pharmaceuticals, and several other types of products.
What is packaging ? Packaging is the science, art, and technology of enclosing or protecting products for distribution, storage, sale, and use. Packaging also refers to the process of design, evaluation, and production of packages. It is the process by which pharmaceuticals are suitably placed so that they retain their therapeutic activity from time to time of their packaging till they are consumed.
Objective of packaging Presentation Identification ,information protection Convienence,complaince Containment during storagepreserves of integrity ofproducts
Types of packaging • Direct contact with primary product • Maintain product quality • Contains product and secondary primary pack • Presentation, protection • Transport shipping tertiary ,warehouse storage, bulk handling
Packaging design Proprietary name Dose Approved name of API Uses Usage instructionPrescription drugs-straight forward designOTC drugs-distinctive design
Why are required packaging designs- Product quality must be maintained. Customers must be able to easily access and use the product without harming themselves or contaminating the product . The component manufactures must be capable of making the components to the required specifications. The pharmaceuticals equipment must be capable of handling the components & maintaining product quality & production efficiency. All aspects of a pack development that may give rise to quality problems must be identified & minimized by good design. One suitably experienced person should be assigned the responsibility of designing a pack . This packaging design coordinator must be fully aware of the involvement required by marketing, quality assurance & production.
Component shape and dimensions There may be product-specific design requirements in some instances,but there are many components that can be standardized, such as ampules, vials, cartons ,labels and leaflets. There will be variety of sizes of components, but again the same shape could be used with different dimensions. There are several adv. to standardizing components-1. Minimizing the packaging validation trails.2. Enabling large quantities of unprinted components to be ordered at a time.3. Reducing the numbers of packaging machine changeover fordifferent types of pack.
4. Shortening the lead time.5. Allowing more utilization of the packaging equipment.6. Fewer component drawing will be required to reducing theadministrative work in preparing, updating &distribution drawing.7.Reducing inventory. Nonstandard production components will probably be more expensive to buy.
Marketing involvement- Consultation with marketing staff should take place when a basic, practical design has been developed. They may help sell OTC pharmaceutical products, although the prime consideration must be the product safety and security. Once a final product has been agreed ,the emphasis should be on minimizing the variations of packs for different markets. One possible method of minimizing variations is to provide a product prospectus to the sales staff.
Packaging validation trials- Prepare a validation protocol detailing all the tests required and standards to be maintained. An eq-foiling and packaging of the tablets(heat sealing operation by methylene blue),determined the methods and rate of monitoring for each operation to ensure that the quality is satisfactory. Extremely hygroscopic tablets may pick up the moisture during foiling ,therefore foiling may require humidity controlled conditions. the replacement of equipment on a packaging line with updated or modified equipment will require the revalidation.
Material of construction The main reason for the tight control over container manufacture is to ensure that changes are not made that can cause product degradation, particularly if the product is liquid. Authorities such as the FDA and overseas licensing authorities will require such details before a manufacturing license is issued. A good example to consider is a plastic bottle containing a product.
Component/product validation- Product stability studies will identify the effect of the moisture ,light and compatibility studies . The following two examples show the approach required for 1. sterile product 2. nonsterile productSterile product/pack validation To start with, the components and products to be used must be full tested and passed the relevant specifications. Each components must be validated through washing and sterilization stages. Then the developing work required relating to the pack would be as follows- a-product and pack compatibilty b-seal integrity
Non sterile product- Non sterile product may still require extensive trials to ensure it’s suitability for the market. If moisture –sensitive tablet packaged in a polypropylene screw- cap bottle, the following validation work will be required. a-water vapor permeabilityBottle wall permeation bottle and cap permeation b-light transmission c-product/pack stabilty
Product considerations The product must be carefully considered during packaging design. The packaging operation can be influenced if the tablet is the wrong shape for filling /packaging equipment concerned.in which table shape and pack are closely related. The adv. & disadv. Of both marketing & packaging must be carefully considered before a final decision is made.
Customer usability Customers must be able to open the pack & remove the contents without harming themselves or contaminating product. If a product contained glass ampule must be capable of being opening without the ampule breaking & without the customer cutting the finger.
Print requirements The artwork must be checked by a competent person, who is fully aware the labeling, regulations, product details ,& the implications of any mistake missed. The print color should be chosen carefully. When dispenses the product, a label is usually placed on the container or carton ,detailing the dosage form & any other special instructions. Allowing a blank space on the pack for the pharmacist’s label is worth considering when designing the artwork.
Regulatory requirements- Prior the sale of the product, the regulatory requirements of the country in which the product is to be sold must be met. The whole issue of regulatory requirements can be difficult to understanding in deciding what is required for new products, how it is to be presented & what changes to processes require notification to the authorities .The main requirements are as follows-1. New drug application(NDA)This must be submitted & prior to the sales of the product on themarket.2.Supplemental new drug application type 1-This must be submitted when major process changes are required.
The supplemental NDA must be approved before the changes takesplace.3. Supplemental new drug application type 2-This is a change important enough to require a supplement butdoes not require FDA approval prior to implementation.4.Annual NDA reports-A report must be submitted that details the changes that havetaken place over the year that do not require a supplementalapplications.5.Drug master file- It is not legally required that a pharmaceutical company submit a DMF. DMF is a submission to the FDA that may provide detailed information about facilities, process or articles used in the
packaging ,manufacturing, processing and storage of one or morepharmaceutical products for human use.
Component specificationsThe main specifications requirements are the componentsdrawing, artwork (printed components only),& the quality tests &standards.A.Component drawingThe best method for preparing a component drawing is to use acomputer system. This will enable rapid preparation & updating ofdrawing.Several rules should be observed-1-the following details should be stated-a) Explicit title.b) Specific reference code & version number.c) Date from which drawing is to become impactive.
d)Component specification reference numbere)Material of constructionf)Terminology used, that is the description of each point ofmeasurement.g)Dimensional limits & units.2-A circulation list for each copy of drawing should be available .3-Enlarge areas of the component drawing to clarify dimensionaldetails when necessary.4-index each dimension with a number on the drawing to preventmistaking them for dimensional data .5-complete drawing must be checked to ensure that all the detailsare correct.These rules are completely understood, hence minimizing thepossibility of errors.
B- Artwork There must be no errors on the completed artwork. The artwork is the prime reference document for the pharmaceutical company quality assurance staff & the supplier. Several rules should be adhered to-1. A specific reference code & version number should be assigned on the artwork. Whenever artwork is modified ,the version number must be changed.2. A circulation list should be available for each copy of the artwork.3. The date at which the artwork is to become effective is required.4. Suppliers must not be allowed to prepare their own artwork from the master supplied by pharmaceutical company ;this can lead to artwork errors. The artwork should be computer generated.
5. The artwork should be color separated.6.Stick –on lettering on the artwork should be avoided .7.The exact position of the artwork text ,color bands & figuresshould be shown in relation to the component.8.Print size & type to be used need careful consideration.9.Type & color of ink to be used must be stated.10. any changes are made to the artwork that render the old versionunsuitable for use.
C.Quality control testing & standards If a serious compliant or a product recall occurs ,the batch system will help determine the problem source & identify the suspect material on the market. There are two classes of components- 1-Primary-in contact with product eq-ampules,vials,plastic bottle,polymer-coated foils2-Secondary-eq-cartons, labels, leaflets Basic testing are same for both types of components, but additional testing for primary testing such as component compatibility & chemical testing. Both must be tested during manufacture (in process control) to ensure the best quality of product.
The critical parameters requiring control need defining-1. Setting the standards- several distinct areas : a) AppearanceCritical major minor(unacceptable (acceptable at (acceptable atAt any levels) low levels) higher levels)
b. Dimensions1.Critical 2.NoncriticalRequiring close control necessary to maintainto ensure that the component component shape but notfunctions correctly requiring close control.
3. Measuring components It is not possible to accurately measure components without trained staff & variety of measuring equipment such as micrometers,callipers & an optical projector. Prior to purchasing equipment ,make sure that equipment is reliable ,easily calibrated ,& is of known precision & accuracy throughout it’s measuring range.
4. Precision and accuracy Once a measuring technique is clearly defined. Next aspect to consider to consider is the equipment precision & accuracy . First ,a set recently calibrated gauging blocks are required (from reputed source),together with a certificate of calibration.
5. Measurement standards- Type of measuring equipment, & calibrated ,it is necessary to decide the number of components to be measured & the standards to be applied.Molded components non molded componentsPVC components glass ampules, tubular, vials ,collapsible aluminum or laminated tubes
6.Computerization of measuring equipmentThere are several advantage to computerization- Prevention of operator transcription errors. Rapid recording of all results Audible indication when results are outside limits(if required) Instant computer statistical calculation & printout of results Printout in a standard work book format Inclusion of measuring instructions.
c. compatibility & customer usability Checking that each component forming a pack fits together & functions correctly. Good example is eye dropper. The nozzle must have a good interference fit into bottle & allow one-drop-at-a-time delivery through the hole in the nozzle when inverted ,but must not leak from the fitted position.
d. Chemical testing The majority of chemical testing is required on primary components. Product degradation or contamination may occur if wrong construction material or unacceptable contaminants are present. Type of testing required depends on the type of component used-(1)Glass vials & Ampules-the USPXXII requirements for glass container are chemical resistance and light transmission.(2)Plastic primary components-requiring both biological &physiochemical tests, because plastic components contain othersubstances such as plasticizer ,stabilizers ,antioxidants ,pigments,lubricants & possibly residues from polymerization.
D. Component specification layout There is a tremendous amount of information to include in the specifications. Rather than having to reissue the whole specification when any of the above changes are necessary. It’s suggested that component specification be split into four parts as follows-1- General specification ,which states the appearance standards,labeling requirements , packaging & transportation details,& labtesting standards & techniques as well as any other items that arenot likely to change very often. Should have a reference number.
2-The artwork should be a separate document, with a referencenumber included on the artwork.3-The drawing for a component should also be a separatedocument ,with a drawing reference number.4-The testing methods for both chemical & dimensional checkswill be general documents, relevant possibly to a whole class ofcomponents eg-carton,vials,labels. The splitting of the specification into four separate units making updating much easier. Standardization with a basic component design will make this layout & system of issuing a specification all the more useful.
References- Annex 9,Guidelines on packaging for pharmaceutical Product, WHO Technical Report Series, No. 902, 2002. Pharmaceutical Packaging Technology by Dixie A. Dean, Roy Evans, Ian Hall. Quality Control of Packaging Materials in the Pharmaceutical Industry By Kenneth Harburn Published October 26th 1990,Taylor & Francis.H. Lockhart, F. Albert Edward J. Bauer W. A. Jenkins