NEPALESE PHARMACEUTICAL INDUSTRIES AND WORLD HEALTH ORGANIZATION RECOMMENDED GOOD MANUFACTURING PRACTICES (WHO GMP) Jaya Bir

Karmac arya (MBA! MP arm)

Ma"a#$r! Fac%&ry O'$ra%i&"(! Om"ica

Introduction Dramatic changes are occurring in the 21st century pharmaceutical industry. Transition creates uncertainty, with both increased risk and increased opportunity. Drug development and time-tomarket remain vital to business success in the pharmaceutical and biotechnology industries, but manufacturing efficiency has become equally important to future success and competitive advantage. a!or business drivers include increasingly crowded therapeutic categories, powerful and increasingly global competition, weak new product portfolios, increasing regulatory requirements that new pharmaceutical products be proven both safe and effective before they can be marketed and sold. Today the success of a pharma company depends on the quick market growth of a newly launched drug to get the cash back for the development. The market success of the ne"t generation of drugs will depend on the interest of the customers and the worldwide penetration from the very first moment. The Global Pharma Market The global pharmaceutical market is growing with sales of #$%$ billion in 1&&& to the sales of #''( billion in 2((% with growth of )* compared to previous year. +orth ,merica accounted for nearly %' per cent -#2%.bn/ of worldwide pharmaceutical sales, reinforcing its position as the world0s largest market, and was also the fastest growing of the top three regions with a rise of . per cent. The 1uropean 2nion ranked second with #1%%bn, up 3 per cent, while third-placed 4apan managed a more modest 2 per cent rise to #'.bn, reflecting the government-imposed pricing pressures that have dealt a heavy blow to the domestic sector. +on-12 regions of 1urope managed a 12 per cent hike to #.bn, but the biggest increase around the globe was seen in 5hina, up 2. per cent to #&.'bn.

The top five drugs for the year were headed by two cholesterol reducers 6 7fi8er0s #12bn drug 9ipitor -atorvastatin/ and erck : 5o0s ;ocor -simvastatin/ with #'.&bn in sales, <anofi-,ventis
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and Cristol- yers <quibb0s 7lavi" -clopidogrel/ powered into third place from eighth in 2(($ with a $1 per cent !ump to #'bn. ,stra;eneca0s anti-ulcerant drug +e"ium -esomepra8ole/ ranked fourth, followed by 1li 9illy0s schi8ophrenia treatment ;ypre"a -olan8apine/, both with #%..bn in sales. eanwhile, more 0blockbuster0 drugs - those making more than #1bn a year - are biologics. ,mong .2 drugs qualified as blockbusters in 2((%, 11 of them were biologics. @verall, biologics accounted for about 1( per cent of all worldwide drug sales in 2((%. F:D e"pense of pharmaceutical companies as a percent of sales is among the highest of any industry. Top ten ranking pharmaceutical companies spent as high as 1) to $(* of their sales in F:D with the amount of #2.'b-#&b per annum. The question of why drugs cost so much is often asked. The answer is often related to the amount of money needed to develop a drug and bring it to the market. This is now surpassing #1 billion per drug. Nepalese Pharma Market =n 1&)&, the importation of drugs was estimated to be worth #1.' millions and there were only about %(( medical shops. ,ccording to another study conducted in 1&.. the importation of drug was #' million. <ubsequent study in 1&&2 showed drugs consumption worth #2( million -sales value/. ,t present there are about 11,((( drug retailers and wholesalers in the country. Though the pharmaceutical industries started in seventies, increase of industries began in the eighties. ,t present, there are about %( pharmaceutical industries in operation in +epal. The study by 7harmaceutical ?ori8on of +epal -7?@+1/ shows the consumption of allopathic drugs in the fiscal year 2('3G(') -1&&&G2(((/ has been #)& millions. The annual increment of consumption has been 1...*. Twenty si" percent of the consumption is met by national industries and rests are being imported mainly from =ndia. The e"pected growth of pharmaceutical consumption by year 2((' is #1.3 million.
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General Background of Nepalese Pharmaceutical Field =n +epal, pharmaceutical companies have been developed since 1&)1. The regulatory act, the Drugs ,ct 1&)., was passed and promulgated on 2'th @ctober 1&).. Hor implementation of the Drugs ,ct, the Department of Drug ,dministration -DD,/ was established in 1&)& and regulatory norm, the 5ode on anufacture of Drugs, was developed only during 1&.%. DD, is taking active role in enforcement of drug regulatory norms under inistry of ?ealth.
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,fter establishment of the DD,, every effort has been made to regulate the pharmaceutical industry to operate with effective implementation of >orld ?ealth recommended Aood anufacturing 7ractices ->?@ A 7/. >ith stringent regulatory norms +epalese pharmaceutical industries are in the process of obtaining >?@ A 7 certification. DD, had initiated the enforcement of A 7 norms as guidelines for few years and planning to make the norms as mandatory by ne"t couple of years. Manufacturing "trength 7harmaceutical industry in +epal can be described as mainly formulating of active ingredients and packing into finished drugs in various solid oral dosage forms. +epalese 7harmaceutical industry includes the supply of pharmaceutical products from +epalese and overseas suppliers. ,ll the private pharmaceutical companies in +epal are family owned business e"cept few. The manufacturer directly imports the active materials required for the production of drugs from =ndia and third countries. There e"ists a separate sector of traders which imports finished products mainly form =ndia and third countries. The local manufacturers supply the finished products to the domestic market only. The system of subcontract manufacturing is not very much popular in +epalese pharmaceutical companies. +epalese pharmaceutical manufacturing industries had long e"perience of last three decades in the field of formulation developments. The +epalese industries are being able to manufacture about 23 percent of total market covering mainly oral dosage forms such as tablets, capsules, solutions and suspensions. The product range covers anti-infective, antipyretic, analgesics, haematinics, vitamins, antacids and ant-allergic. ,bout %( national industries and in operation and couple of companies are in pro!ect phase. @ne of the ma!or constraints of the +epalese pharmaceutical industry is the strong investor with good intension of establishing pharmaceutical industry importing new technologies and e"tending its market internationally. >ith recent consent of >T@ as member, +epal is getting ready for liberal market policy with competition based on standards. =n this contest the regulatory body DD, is making all required preparation to uplift pharmaceutical industry standard to >?@ A 7 level to enhance their capability to sustain competition. >ith collaborative efforts all sector five private +epalese pharmaceutical companies had shown their capability to achieve >?@ A 7 certification from DD,. The >?@ A 7 certification would open its pharma e"port market to good number of <outh ,frican and other countries. >ith liberal economic policy +epalese government also encourage foreign investment with required protection and support. Manufacturing #cti$ities The +epalse pharmaceutical industry0s manufacturing costs are relatively lower than those of generic manufacturers in the >est. This is primarily due to lower labor and infrastructure costs. >ith its strength of formulation development in the products mentioned +epalese pharmaceutical companies have good opportunity to cater the international market. >ith the neighboring country =ndia having strong competency in pharmaceutical field, +epalese pharma industry have easy access to required technology, equipment and materials. <o =ndia is one of ma!or supplier for pharmaceutical industry in +epal. +epalese industries also deal with other countries for importing raw material and some equipment.
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Concept of %ualit& Management "&stem ?istorically end product testing is considered as key to pharmaceutical product quality. Traditionally in the pharmaceutical industry, the quality function is divided into two parts, quality control and quality assurance. Iuality control centers on testing products to assure their compliance to specification. =t is in general concerned with evaluating events from the past. DD, has recogni8ed this deficiency with the often-quoted philosophy that JIuality should be built into the product, and testing alone cannot be relied on to ensure product qualityK. Iuality assurance is focused on building quality into a product through activities like validation, process and environmental control, and documentation. @nly relatively recently has the pharmaceutical industry begun to emphasi8e a quality management accountability for continuous improvement of processes, people, and culture. Iuality management is about the future, about prevention, and management0s role in improving the quality system. The +epalese pharmaceutical companies had already started the process of change to inherit their traditional approach on quality with the modern concept of quality with belief that quality is never an accident. =t is always the result of high intentions, sincere efforts, intelligent direction and skillful e"ecution. The !ob of quality management is not !ust advising a sampling plan for the acceptanceG re!ection of the incoming materials or products and controlling manufacturing process conditions. =t is in fact a !ob at every stage of the company0s activities. Iuality anagement is a company wide activity, involving the combined efforts of various departments such as F : D, engineering, purchase, production, Iuality 5ontrol, Iuality ,ssurance, ?uman Fesources, arketing, Distribution, >arehouse, etc in different phases with a view to achieve the desired quality of the end product. Iuality awareness must begin at the very conception of the product and continue through various stages of development and manufacture and even during its use to get feedback from the users, which is essential for continuous product improvement. %ualit& of Medicine: 'ocall& Manufactured Vs Imported , medicine to claimed, as quality product must have following characteristicsL M Identit&(The correct active ingredient is present. M Purit&(The drug is not contaminated with potentially harmful substances. M Potenc& (The correct amount of active ingredient is present, usually between &' and 11( percent of the labeled amount. M )niformit&( 5onsistency, color, shape, and si8e of the dosage form do not vary. M Bioa$ailabilit&( Cioavailability refers to the speed and completeness with which an administered drug enters the blood stream. This must be consistent to provide a predictable therapeutic result. Drug bioavailability differences e"ist between manufactures of the same product. Therefore, careful evaluation of generic drugs may be necessary before purchase and use. M "tabilit&(The activity of the drug is ensured for the period of time stated on the product label, that is, until the e"piration date. M Pharmacopoeial "tandard(, drug is of good quality if its characteristics meet the standards described in a widely accepted pharmacopoeia such as the Critish 7harmacopoeia -C7/,
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1uropean 7harmacopoeia, =nternational 7harmacopoeia -=7/, or -2<7/.

2nited <tates 7harmacopeia

>ith strong regulatory enforcement of >?@ A 7 certification requirement for restriction of import and marketing products manufactured outside the country had resulted in phase out of many products, which are being market earlier comfortably. This had clearly indicated that all the imported products available are not of the e"pected standard. @nly those products with required standard are allowed to remain in the market. This had opened the eyes of patients, prescribes and pharmacist to be cautious about the use of medicines available in the market. @n the other hand the close monitoring of national manufacturersN towards stringent implementation of >?@ A 7 norms in manufacturing medicines had resulted in enhancement in quality of the medicines manufactured locally. This requirement had also made the national pharmaceutical companies to develop their technical competency to achieve the >?@ A 7 requirements in strict sense during manufacturing process on one hand and to face the competition in the market with imported products on the other hand. =n this connection of development and competition, last year five +epalese pharmaceutical companies had got the success in getting >?@ A 7 certification from DD,. ,s >?@ A 7 certification is a well-accepted global concept to assure production of quality medicines, this had given good confidences among the prescribers and users towards the use of medicines manufactured by national companies. This development also had proved the competency of professionals and commitment from higher management in effective implementation of >?@ A 7 norm for manufacturing quality medicines. The national companies are under close supervision of control of regulatory authority and any shortfall made can be identified and corrected with very short span of time. The regulatory body can enforce the stringent regulatory norms with the ob!ective to develop those who can meets the requirements and to phase out those who fails to meet the requirement. This give serious concern for the companies to follow the regulatory norms strictly to have their e"istence in the market. Cut in case of imported products, the monitoring product quality requirements are done based on documented evidence only. This may restrict in monitoring the manufacturing operation closely skipping to notice if any shortfall is being practiced at factory during manufacturing operation. <ome companies may not act with the required e"tent of seriousness with DD, requirements, as even if they loose their market presence in +epal, their e"istence is not at risk. ,bove-mentioned facts had been reflected in good growth in the acceptance of medicines manufactured by national pharmaceutical companies. The pharmacists, other professional and higher management had gained their confidence and e"pressed their commitments in developing the industry standards. ?owever every one had strong challenge and responsibility to develop every manufacturing unit to equal level of >?@ A 7 standards so the every product manufactured by national companies shall be claimed to be manufactured as per >?@ A 7 certification requirements. "cope for In$estment and *e$elopment of Pharmaceutical Industr& in Nepal +epalese companies need to attain the right product-mi" for sustained future growth. 5ore competencies will play an important role in determining the future of many +epalese
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pharmaceutical companies in the post product-patent regime after 2(('. +epalese companies in an effort to consolidate their position will have to increasingly look at merger and acquisition options of either companies or products. This would help them to offset loss of new product options, improve their F:D efforts and improve distribution to penetrate markets. The simplified regulatory norms for those who are coming up with all required concept would of one of biggest advantage for foreign investment. The DD, also allows manufacturing latest drug molecule if one can provide sufficient evidence of safety and better efficacy over the similar e"isting drug. Fesearch and development has always taken the back seat amongst +epalese pharmaceutical companies. =n order to stay competitive in the future, +epalese companies will have to refocus and invest heavily in F:D. The +epalese pharmaceutical industry also needs to take advantage of the recent advances in biotechnology and information technology. The future of the industry will be determined by how well it markets products to several regions and distributes risks, its forward and backward integration capabilities, its F:D, its consolidation through mergers and acquisitions, comarketing and licensing agreements. The F:D activities may as well be developed with =ndustry,cademic collaborative works. The upcoming company with good backup of research and development would have easy and comfortable stay and sustainability in the +epalese pharma market. Conclusion Iuality is fundamentally about customer focus. Coth the pharmaceutical industry and the DD, have this in commonB their customer is the patient. >hile quality control and quality assurance are important, best quality practice today emphasi8es the management of the quality system. The quality system consists of important processes, highly skilled people, and an empoweringGmotivating culture. Training of personnel at all levels must be a priority for management. , model of a quality system with the specific requirements of >?@ A 7 is required to achieve quality. 5ontinuous improvement of the quality system is assured by having an effective quality planning process. ,ll employees must take responsibility for the quality of their work. , critical but difficult process is communication. anagement must provide the direction -top6down/, listen -bottom6up/, and encourage cross-functional cooperation. =t is clear that quality depends on the leadership of the organi8ation

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