The term labelling, means all the labels and other written, printed, or graphic matter upon an immediate container of an article or upon, or in, any package. The awareness for quality brands has been risen to all time high; whether it is a pharmaceutical product, domestic product, consumer product or food product and other consumables. The Government as well as regulatory authorities have imposed different regulations and made mandatory for all manufacturers to label their product well clearly and print all the information that might be required by the consumer. The Labels and Labelling is part of the packaging operation. It introduces the product to the consumer with the understandable information and also catches his awareness on the product. All the vital, mandatory and strategic information, and operating/ consuming instructions, have to be clearly printed on the product. Therefore, the labelling is an important function.
A good labelling gives good impression to the patient/consumer. It is also an advertising media for the product, which will attract the consumer/ patient. However the labelling/Packaging is one area that has been strongly neglected by the pharmaceutical industry as a whole.
The labelling/packaging of drug product have to display : Identity of the product/drug and strength
*Protection in terms of storage.
*Shelf life.
*Dosage requirement.
*Any precautionary measure.
*Adverse Reaction.
*Pack size.
Where as the Patient Information leaflet (PIL) or literatures identifies the product together with its active ingredients, pharmacotherapeutic group, information needed for taking the drug, dosage, special warnings etc. This article describes the labelling requirements, issuance, control, counterfeits and other trends only of finished products.
Labelling Requirements
As per the US Pharmacopoeia, the following approach will be followed for the labelling of dosage forms.
Amount of ingredient per dosage unit: The strength of a drug product is expressed on the container in terms of micrograms or milligrams or grams or percentage of the drug substance, whichever form is used in the title, unless otherwise indicated in an individual monograph. Both the active and drug substance names and their equivalent amounts are then provided in the labelling. The pharmaceutical drug products not in unit dosage form shall be labelled to express quantity of each active ingredient in each mL or in each gram.
In order to minimize the errors in dispensing and administration of drugs, the quantity of active ingredients shall be shown without decimal point that is followed by terminal zero (Eg: express as 4mg (not 4.0mg).The quantity of active ingredient when expressed as a decimal number smaller than 1 shall be shown with 0 preceding the decimal point Eg: express as 0.2mg (not .2mg).Labelling of salts of drugs: It is an established principle that pharmacopoeia articlesshall have only one official name, for purpose of saving space on labels and because chemical symbols for most common inorganic salts are well known to doctors and pharmacists as synonymous with written forms .The following alternatives are permitted : HCl for hydrochloride, HBr for hydrobromide. The symbols Na and K are not used where word Sodium or potassium appears at the beginning of the official title, for example Phenobarbitle Na is acceptable but NA salicylate is not to be written.
Labelling of vitamin containing products: The vitamin content of an official drug product shall be stated on the metric units per dosage unit. The amounts of vitamins A,D, and E may be stated also in Pharmacopoeial units.Labeling of Parentral and topical Preparations: The label should state the names of the all added substances and in case of parentral preparations, also their amounts or propotions, except that for substances added for adjustment of PH or to achieve the isotonicity, the label may indicate only their presence and the reason for their addition.
Labelling electrolytes: The concentration and dosage of electrolytes for replacement therapy shall be stated on the label in mill equivalents (mEq).Expiration date: The Label of an official drug product shall bear the expiry date so that it can be read by an ordinary individual under customary conditions of purchase and use. It is displayed in high contrast to the background or sharply embossed and it is easily understood.
The recent FDA guidance for industry released in September 2006 states, the packaging and labelling controls, critical stages in the pharmaceutical manufacturing process, are not specifically addressed in quality systems models. However, the Agency recommends that manufacturers always refer to the packaging and labelling control regulations at 211 Subpart G.
In addition and this is consistent with modern quality systems - FDA recommends that, as part of the design process, before commercial production, the controls for all processes within the packaging and labelling system be planned and documented in written procedures. The procedures should outline quality control activities and the responsible positions. Specifications and controls for the packaging and labelling materials should also be determined before commercial production. Distinct labels with discriminating features for different products, such as a product marketed with different strengths, should be included to prevent mislabelling and resulting recalls.
*Strict control shall be exercised over labelling issued for use in drug product labelling operations. The control procedure used should be in writing with sufficient detail. Labelling materials issued for a batch shall be carefully examined for identity (with material code) and conformity to the labelling specified in the master or batch production records.
*All materials and products must be easily identifiable to ensure that only the correct materials are used.
*There is accountability in terms of the numbers of labels issued and used the reconciliation must be documented against a defined limit of acceptability. Labels are handled in a secure manner and applied properly.
*Labels representative of those used in the particular batch and should be included in the batch packaging Record.
*All excess labels bearing batch number related information should be destroyed. Returned labelling shall be maintained and stored in a manner to prevent mix-ups and provide proper identification.
Challenge test: A challenge test shall be carried out during the packing operation once in 6 months to challenge the chemist, operator or packaging personnel by keeping the incorrect labels in the packaging area or module under the supervision of QA and production manager. This test shall be carried out without the notice of the operator, production chemist and QA personnel involved in the packaging activity. This activity shall be documented by writing a challenge test protocol and report. This approach will further enhance the confidence level of the personnel involved in the packaging and organisation, the use of correct label during packing.Training is equally essential for the personnel involved in the packaging operations so that the personnel remain proficient in their operational functions and their understanding the of CGMP regulations.
Label counterfeiting and innovative packaging:
In 2003, FDA announced a mass recall of the cholesterol-lowering drug Lipitor. The recall triggered by the discovery of the counterfeits, affected more than 130,000 bottles. According to FDA, the number of counterfeit drug investigations has raisen from an average of five per year in the 1990s to more than 20 per year since 2000.
Counterfeiting is a huge problem for the pharmaceutical industry all over the world as it relates direct liability. The pharmaceutical industries annually loose billions of dollars to very clever counterfeiters. Widely publicized cases such as the US Lipitor recall have projected the issue of counterfeited drugs into public view. All this attention has trickled down into labelling industry to create innovation in packaging and labelling. These include the hologram security, tamperproof seals, advanced colour bar coding and radiofrequency identification (RFID).
Colour coding: Colour coding used for product differentiation and has been used effectively in few instances for ophthalmic solutions and anaesthetics.Holograms: Act like company seal and offer an alert the consumer a simple to identify the fake from the genuine.
Bar coding: The bar coding is facilitation tool to track the products effectively at any point of time to ensure effective supply chain management and speedy product recall in need. It is also effective means of deterring the scourge of counterfeits and to improve the patient safety is to keep track of supplies made through the supplies made through the supply chain and build up the capability to trace the product from its origin to its sales point. Hence bar coding system for drug products is an error prevention tool.
Bar coding provides for unique identification for products and companies with linkages to the complete and accurate manufacturing history. Now in India most of the FDA approved companies using the bar coding system for all export products (US and Europe). Bar coding helps in identification of hospitals, departments, doctors, specialities and every supplies comes in, uses up and goes out.
Apart from health care sector, barcodes are quite popular in all other industry segments like FMCG, other consumer durables. Sometimes a second bar code may be on a container for internal label identification. This can't be used for product tracking and some manufacturers some manufacturers encode the NDC (National Drug coding) in Code 128 on Blisters.
EAN coding systems: The Pharmaceutical industry uses world wide uses EAN 13 bar code system, which stands for European article numbering. In India it is a registered society. It has three digit country code to start with, for it is 8901.This is followed by the company code with product information codes capturing history of products. The system offers flexibility to contain as mush as 8 - 10 lakh products.
Radiofrequency identification (RFID): A latest technology that allows for multiple chips to be scanned simultaneously has made headline for its usefulness in the logistics industry. But it also gaining notoriety for role it can play in the pharmaceuticals supply chain. That is tracing individual pharmaceuticals to make sure they come from and stays with legitimate source. At present RFID is in its early development in the pharmaceutical industry, most likely in next coming years it could have effect on the direction that the industry goes regarding variable information labelling and in the long term it will have a major effect.
Paperless Labels, white Labels: While currently there is trend towards extended text labels, there is also move in industry for the opposite. The Pharmaceutical Research and Manufactures of America (PhRMA) will soon be launching a trail of its paperless labelling initiative. After successfully testing it at 10 Pharmacies, PhRMA plans to bring the trail to 264 pharmacies for a larger test. In this system the drug information is available on the internet and patient can access a web site and download or print out the information. The association has publicly stated that full electronic dissemination of labelling information is the ultimate goal. However the labels won't be eliminated together.
Conclusion
As with any market new technologies will come and go. But one thing remains a constant within the pharmaceutical industry is the need for the quality. If a label is not manufactured correctly, it could lead implications in the form of human and financial losses. A quality packaging to drug is what head to the brain. Hence it is the sole responsibility of the manufacturer to use the right label for the right product.
The author is Asst.Manager -
Quality Assurance.Natco Pharma Limited.Hyderbad.
E-mail: gireesh31@gmail.com